Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22092 | 66499;66500;66501 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| N2AB | 20451 | 61576;61577;61578 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| N2A | 19524 | 58795;58796;58797 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| N2B | 13027 | 39304;39305;39306 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| Novex-1 | 13152 | 39679;39680;39681 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| Novex-2 | 13219 | 39880;39881;39882 | chr2:178582095;178582094;178582093 | chr2:179446822;179446821;179446820 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs192182734  |
-1.647 | 0.317 | N | 0.649 | 0.306 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 4.14E-05 | 1.13161E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 1.40726E-04 |
| L/F | rs192182734 |
-1.647 | 0.317 | N | 0.649 | 0.306 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs192182734 |
-1.647 | 0.317 | N | 0.649 | 0.306 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/F | rs192182734 |
-1.647 | 0.317 | N | 0.649 | 0.306 | None | gnomAD-4.0.0 | 6.81962E-06 | None | None | None | None | N | None | 1.33419E-05 | 1.33382E-04 | None | 0 | 0 | None | 0 | 0 | 8.47817E-07 | 0 | 1.60113E-05 |
| L/R | rs1553627146 |
None | 0.484 | D | 0.797 | 0.462 | 0.657140475542 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8155 | likely_pathogenic | 0.7987 | pathogenic | -2.972 | Highly Destabilizing | 0.035 | N | 0.625 | neutral | None | None | None | None | N |
| L/C | 0.894 | likely_pathogenic | 0.8954 | pathogenic | -2.045 | Highly Destabilizing | 0.824 | D | 0.745 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -3.767 | Highly Destabilizing | 0.38 | N | 0.821 | deleterious | None | None | None | None | N |
| L/E | 0.9949 | likely_pathogenic | 0.9941 | pathogenic | -3.448 | Highly Destabilizing | 0.38 | N | 0.767 | deleterious | None | None | None | None | N |
| L/F | 0.9009 | likely_pathogenic | 0.8987 | pathogenic | -1.789 | Destabilizing | 0.317 | N | 0.649 | neutral | N | 0.510293682 | None | None | N |
| L/G | 0.986 | likely_pathogenic | 0.9835 | pathogenic | -3.568 | Highly Destabilizing | 0.38 | N | 0.761 | deleterious | None | None | None | None | N |
| L/H | 0.9951 | likely_pathogenic | 0.9947 | pathogenic | -3.191 | Highly Destabilizing | 0.915 | D | 0.837 | deleterious | D | 0.522068061 | None | None | N |
| L/I | 0.1282 | likely_benign | 0.1235 | benign | -1.168 | Destabilizing | 0.009 | N | 0.567 | neutral | N | 0.426027214 | None | None | N |
| L/K | 0.9935 | likely_pathogenic | 0.9931 | pathogenic | -2.422 | Highly Destabilizing | 0.38 | N | 0.725 | prob.delet. | None | None | None | None | N |
| L/M | 0.4812 | ambiguous | 0.4654 | ambiguous | -1.24 | Destabilizing | 0.38 | N | 0.589 | neutral | None | None | None | None | N |
| L/N | 0.9963 | likely_pathogenic | 0.9959 | pathogenic | -3.147 | Highly Destabilizing | 0.555 | D | 0.832 | deleterious | None | None | None | None | N |
| L/P | 0.9878 | likely_pathogenic | 0.9835 | pathogenic | -1.762 | Destabilizing | None | N | 0.682 | prob.neutral | N | 0.510547171 | None | None | N |
| L/Q | 0.9863 | likely_pathogenic | 0.9837 | pathogenic | -2.812 | Highly Destabilizing | 0.555 | D | 0.799 | deleterious | None | None | None | None | N |
| L/R | 0.9872 | likely_pathogenic | 0.986 | pathogenic | -2.371 | Highly Destabilizing | 0.484 | N | 0.797 | deleterious | D | 0.522068061 | None | None | N |
| L/S | 0.9883 | likely_pathogenic | 0.9867 | pathogenic | -3.668 | Highly Destabilizing | 0.38 | N | 0.725 | prob.delet. | None | None | None | None | N |
| L/T | 0.8648 | likely_pathogenic | 0.8472 | pathogenic | -3.192 | Highly Destabilizing | 0.081 | N | 0.586 | neutral | None | None | None | None | N |
| L/V | 0.0998 | likely_benign | 0.0922 | benign | -1.762 | Destabilizing | None | N | 0.313 | neutral | N | 0.396026807 | None | None | N |
| L/W | 0.993 | likely_pathogenic | 0.991 | pathogenic | -2.215 | Highly Destabilizing | 0.935 | D | 0.794 | deleterious | None | None | None | None | N |
| L/Y | 0.9915 | likely_pathogenic | 0.9911 | pathogenic | -2.019 | Highly Destabilizing | 0.555 | D | 0.714 | prob.delet. | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.